The five histone genes of Drosophila are grouped together in a unit that is repeated 100 times per haploid DNA complement. The repeats are clustered in the 39DE region of the salivary map. The molecular organization of the histone genes is well characterized. However, the minimum number of histone genes required for viability has not been defined, nor has it been determined if each repeat unit carries the same genetic information. Whether these units are regulated differentially during development is also not known. The objective of this proposal is to dissect genetically the Drosophila histone gene cluster by deficiency and point mutant analysis. I have recently constructed chromosomes bearing either total or partial deficiencies for the histone genes. These deficiencies are being used to screen mutagen-treated chromosomes for recessive lethal lesions in the histone region. A complementation map, based on lethality, will be defined using all the recovered lesions. This map will then be extended by an analysis of the phenotypes of lethality using among all lethal combinations of chromosomes. The pattern of complementation will reflect the genetic consequences of histone gene redundancy, and this pattern can not be predicted at present. DNA from stocks carrying new lethal-bearing chromosomes will be examined by restriction enzyme analysis. The deleted DNA segments will thus be defined and in this manner, the genetic properties of the histone genes will be correlated with the DNA sequence organization.